Carotenoids exist widely in nature. Pigment in carbohydrates form was firstly crystallized and separated from the carrot roots by Wachenroder in 1831 and named as “carotene”. After that, yellow polar pigments are separated and extracted from autumn leaves by Berzelius and named as “xanthophyll”. With the development of biophysical technology, a series of natural pigments are separated by chromatographic method and named as “carotenoid”. They have common chemical structural characteristics, and their molecular centers are all long chain of polyunsaturated polyisoprene. Many derivatives are produced by the means of cyclization, addition of oxygen or rotation of bond and isomerization. Currently, members of known carotenoids have about more than 600 species.
There are hundreds of carotenoids existed in the nature, but there have six species to be common and relatively large amounts, such as β-carotene, astaxanthin, canthaxanthin, lutein, zeaxanthin and lycopene. With the development of biotechnology and synthesis technology, many species of the six carotenoids have many different origins, for example, β-carotene may be obtained by synthesis, and also by fermentation method or cultivating Dunaliella, and also by extracting from natural substances, such as palm oil. Lycopene may be obtained by extracting from tomatoes or by fermentation, or also by synthesis. In these carotenoids, lutein is an exception, currently lutein is only obtained by extracting from plant but not by high cost synthesis method because of asymmetrical structure.
These six carotenoids which have similar molecular structures are a kind of hydrocarbons and oxygenated derivatives thereof. They are composed of eight isoprenoid units and only have small differences in a six-member ring at two ends. There are many chromophoric groups with conjugated double bond in the molecular structure of carotenoids, which gives carotenoid a special absorption area (blue light area) in ultraviolet-visible light area. Accordingly, crystal or solution of carotenoid possesses very glorious red, orange or yellow color under visible light. The color varies with different concentration. Carotenoids are deemed as a kind of pigments for a long time, those in autumn leaves and all sorts of colorful animals give people incomparable aesthetic feeling in nature. Meanwhile these conjugated double bonds also make carotenoid become a good free radical scavenger which has very strong activity of antioxidant and could effectively block free radical chain reaction in the cells. Thus, carotenoid has many kinds of special and important physiological functions.
β-carotene is the most wide and important carotenoids, and is a favourable provitamin A. According to the amount of Vitamin A in body, β-carotene could automatically decompose to supplement deficiency of Vitamin A. Lutein and zeaxanthin are isomers, and the only difference between them is the different site of a double bond on one of the six-member ring chain-terminating. They are only carotenoids existed in the human eye retina, and they are selectively deposited in the macular region and the whole retina, and their density is the highest around the central fovea of macula and gradually decreased around the retina. These macular pigments are able to effectively prevent from occurrence of oxidation reaction on the retina and have important protective effect on the retina. Lycopene has very good effect on prophylaxis and treatment of prostate disease. Astaxanthin also has important roles of anti-tumor and preventing cancer, etc. This is why lots of epidemiologic studies confirm that consuming fruits and vegetables containing carotenoid usually and regularly decrease risks of chronic diseases including cardiovascular disease, and meanwhile have beneficial effects on prophylaxis of cancer.
Therefore, nutritionists highly recommend that addition or preventive ingestion of antioxidant such as vitamin and carotenoid. Food and pharmaceutical market provide consumers a great quantity of the kind of “cell protective agent”. Now various health foods added to single or many kinds of carotenoids are presented on the market, but the more effective means to supplement carotenoids for people is to ingest the materials in the form of dietary supplement, for example various tablets, hard capsules, soft capsules, etc. Usually only a grain of tablet or capsule can fulfill a day total requirement of carotenoid for one person. Concerning request of these ingestion way, many kinds of dosage forms of carotenoid are also presented on the market, for example microparticles CarolBeta® and CaroCare® rich in β-carotene, microencapsulation beadlets CarolGold® , FloraGlo® rich in xanthophyl, microparticle CarolZea® rich in zeaxanthin, microparticle Redivivo® rich in lycopene, etc. are suitable for tabletting or hard capsules; And there are some carotenoid oil suspensions suited to cover soft capsules. It is more convenient and popular methods by ingesting carotenoids in the form of soft capsules. Carotenoids usually exist in the form of oil suspensions when preparing soft capsules, that is, carotenoids are grinded to a certain degree of fineness and then suspended in a vegetable oil, so the fluidity of carotenoid oil suspensions determines the complexity of a production process. Methods of decreasing the viscosity of carotenoid oil suspensions have been disclosed by related patents.
On the other hand, it is very important for the particle size of the active ingredient in the carotenoid oil suspension, because which directly determines the level of bioavailability of the raw material oil suspension in soft capsule in body, the smaller carotenoid particle size means more easier absorption and utilization in body after ingestion, consequently, the smaller carotenoid particle size has the higher bioavailability. So people always try to reduce the carotenoid particle size in the oil suspension to reach to a level of micron even nanoscale, in order to make it have higher bioavailability after being filled into the soft capsule.
In addition, it is also important that excessive harmful organic solvents should be brought thereinto when ingesting carotenoids in the form of soft capsules. So it requires that organic solvents are used during as few steps as possible before carotenoids are filled into soft capsules and the organic solvents are inevitably used in certain steps removed in extra processes in order to make it meet requirements for human edible safety.
There are many methods of preparing for carotenoid oil suspensions in the previous documents. A common method is to sufficiently grind carotenoid crystals, and then mix the carotenoid powders grinded with a vegetable oil to obtain oil suspensions. However, the carotenoid crystals can't be grinded very fine by using the method, the particle size thereof is about 15 μm. It will eventually affect absorption and utilization of the oil suspension in body, and make the bioavailability more poorer. Besides it will inevitably cause temperature increasing of carotenoid crystals during grinding. Especially the increase of temperature will be more obvious when the particle size of carotenoids should be grinded to very fine, which will inevitably result in degradation and loss of carotenoids due to oxidization of carotenoids resulted from high temperature. So it would be undesirable to prepare for carotenoid oil suspensions by the method of grinding.
U.S. Pat. No. 6,936,279 B2 discloses a method of preparing for carotenoid oil suspensions. In particular, a carotenoid is firstly mixed with a water-insoluble solvent, and then to spray under nitrogen after mixing with a vegetable oil, to collect the sprayed solution and to recycle the solvent to obtain a carotenoid oil suspension. In the process, a large quantity of emulsifier and water are added in order to guarantee carotenoid particles no longer reaggregated after spraying, and then to stop spraying and to recover the solvent after collecting a certain amount of the sprayed “concentrate” in order to remove a large amount of organic solvents. It certainly results in industrial production disadvantageous, for the yield of the method is lower, and consequently the method is only suitable for laboratory preparation. Moreover, it is not very effective for preventing from reaggregation of carotenoid crystals in droplets, and the particle size of carotenoid crystals in oil suspension product is larger. More importantly, it is very difficult for sufficiently removing organic solvents due to existences of a large amount of emulsifier. It will certainly bring hidden trouble in safety of the final product in soft capsules. At the same time, there is no effective subsequent operation to remove the useless emulsifier for preparation of the oil suspension. It will cause waste and increase safety risks.
The present invention tried to find out a method of preparing for a carotenoid oil suspension with higher bioavailability. The carotenoid particles in the carotenoid oil suspensions obtained by the method of the present invention are very fine with the average diameter of less than 5 μm. So it is easily absorbed and utilized in the body, and there is no residual organic solvents in the product, and the product has very higher safety. Moreover, the process has higher industrial production efficiency and is suitable for continuous operations.